Most Transvaginal Mesh Devices Were Approved With Little Evidence

Allowed on market via 510(k) clearance, which does not require clinical studies

Most transvaginal mesh devices were allowed on the market without evidence from a clinical trial, with the first studies published years after initial clearance, an evidence review found.

Sixty-one devices have been marketed based on the FDA's 510(k) clearance of two similar devices in 1985 and 1996, and no clinical trials for these devices were conducted at the time they were cleared, reported Carl J. Heneghan, DPhil, of Oxford University in the U.K., and colleagues.

Moreover, any publication of clinical trials on the safety and efficacy of these devices was published a median of five years after device clearance (range 1 to 14 years), the authors wrote in the BMJ Open.

The 510(k) process does not require that devices undergo clinical testing prior to clearance -- they only have to demonstrate "substantial equivalence" to an already marketed device in terms of design, general function, and intended use. It's been criticized as being excessively lax, allowing products on the market with essentially no validated study.

Transvaginal mesh for pelvic organ prolapse in particular has been controversial, with the FDA issuing a high risk warning on transvaginal mesh products in January 2016, reclassifying them from class II to class III. The authors also cited a Cochrane review that said permanent transvaginal mesh may be associated with "higher rates of reoperation and bladder damage."

Heneghan and colleagues examined the FDA summary database, using the 501(k) clearance of Mersilene Mesh (Ethicon) in 1985 and ProteGen Sling (Boston Scientific) in 1996, and searching on related device clearances.

The authors characterize a "confusing picture," arguing that "newer devices are compared with various older devices, and devices with similar names are compared with each other," and even that some devices had "changes to their indications over time."

They were also unable to find clinical trial evidence for "any of the devices in the 510(k) submissions at the time of approval," they wrote. They traced relevant documentation and the year of clearance for 29 of 33 different mesh products and "in no case was the trial published before approval."

Heneghan and colleagues also retrieved 119 orders for postmarketing surveillance that the FDA ordered from these companies in 2012. These were from 126 different vaginal mesh devices, marketed by 34 different companies, with four companies covering 43% of the orders (American Medical Systems, Boston Scientific, Coloplast Corporation and Synovis Surgical Innovations/Baxter), the authors said.

In two-thirds of these orders, "the manufacturer ceased market distribution of the device subject to the postmarketing surveillance order," while in a quarter of cases, the order no longer applied because the indication had been revised, they said. In fact, less than 10% of orders reported they were doing postmarketing studies.

A separate analysis appearing in The BMJ, also written by Heneghan and colleagues, argued that the process is flawed, noting that "changes in design should have alerted regulators to important differences in the technological characteristics of the mesh that should have negated the use of equivalence" in the approval process.

Moreover, the analysis said, attempts to explore the long-term outcomes of these devices have been stymied by "methodological shortcomings, high drop-out rates, and sparse long-term data."

The authors further state some proposed changes to the regulatory process in their analysis, namely that "long-term implantable devices should have been evaluated in studies with follow-up of at least five years." They also suggested a patient registry "so that any shortcomings can be more readily tracked, patterns of use monitored, and patients later judged to be at risk more easily identified," they said.

Heneghan is an expert witness in a current medical device legal case and has received financial renumeration from an asbestos legal case. He has received support from the FDA and the National Institute of Health Research School of Primary Care, and was a recipient of a grant from the U.K. government.

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